A model of nitric oxide tubulovascular cross talk in a renal outer medullary cross section

Abstract

We developed a two-dimensional model of NO transport in a cross section of the inner stripe (IS) of the rat outer medulla to determine whether tubular and vascular generation of NO result in significant NO concentration (CNO) differences between the periphery and the center of vascular bundles and thereby affect medullary blood flow distribution. Following the approach of Layton and Layton (Layton AT, Layton HE. Am J Physiol Renal Physiol 289: F1346–F1366, 2006), the structural heterogeneity of the IS was incorporated in a representative unit consisting of four concentric regions centered on a vascular bundle. Our model suggests that the diffusion distance of NO in the interstitium is limited to a few micrometers. We predict that, under basal conditions, epithelial NO generation raises the average CNO in pericytes surrounding peripheral descending vasa recta (DVR) by a few nanomoles relative to that in pericytes surrounding central DVR. The short descending limbs and long ascending limbs are found to exert the greatest effect on CNO in pericytes; long descending limbs and short ascending limbs only have a moderate effect, whereas outer medullary collecting ducts, which are situated far from the vascular bundle center, do not affect pericyte CNO. Our results suggest that selective stimulation of epithelial NO production should significantly raise the periphery-to-center DVR diameter ratio, thereby increasing the outer medulla-to-inner medulla blood flow ratio. However, concomitant increases in epithelial superoxide (O2−) production would counteract this effect. This model confirms the importance of NO and O2− interactions in mediating tubulovascular cross talk.